2,4,5-trichlorophenol cyanine dye compound and process for the preparation thereof



U i States Patent .iliiiii of these compounds are known, others can be prepared 3,074,938 by reacting the quaternary ammonium hydroxide with 2,4,5-TRICHL0R0PHEN0L CYANINE DYE an acid. The quaternary ammonium hydroxide can be POUND AND PR S O THE PREPARATION prepared by reaction of the iodide with silver oxide in THEREGF 5 the presence of water. igg f' z g 32 23;, $23 g if j When a 3-ethyl-2-[3-(3-ethyl-2-benzothiazolinylidene) Michigan propenyl] henzothiazolium compound other than the hydroxide is employed as the starting material, one mole- No Drawing. Filed Jan. 29, 1960, er. No. 5,340

1 Claim, (CL 2 0-24055 cular equivalent of the 2,4,5-tr1clrloroph'enol can he 10 present in the reaction mixture in the form of an alkali This invention relates to a novel 2,4,5-t-richlorophenol metal salt. This alkali metal salt of the 2,4,5-tr-ichlorocompound which possesses anthelmintic activity and to phenol can be added to the reaction mixture or produced processes for the manufacture thereof. in sit-u. Suitable solvents tor the reaction are those in More particularly the present invention relates to the which the reactants are at least partially soluble, and novel 2,4,5-trich=lorophenol compound which has the which are relatively non-reactive toward each of the reactants. Reaction media preferred because of satisformula 0- OH S on=on-on S O1 O1 0 0 ILL l o o 2 Ce We a a It is known that the 2,4,5 trichlorophenol possesses factory solvent properties, unreactivity and inexpensiveanthelmintic activity. It is relatively cheap and easily ness .are water and lower molecular weight alkanols. accessible. Its use in human and veterinary medicine is Other satisfactory media can be selected from a wide subject, however, to a number of objections which tend to variety of solvents, particularly those which are neutral lower its value as a useful ianthelmintic agent. In the 9 and .polar. The reaction product may be isolated by difree state, the compound possesses a highly objectionarect filtration, or by filtration following concentration ble taste causing an undesirable burning sensation when of the reaction mixture or dilution with a non-polar solintroduced into the oral cavity. It is also highly irritatvent or with water. ing to mucosal tissue and may produce erosion of the The product of the invention is useful as an anthelminoral cavity and gastric disturbances unless administered tic agent. it possesses a high degree of activity when in dosage forms possessing enteric properties. administered orally to higher animals infested with worms The new 2,4,5-trichlorophenol of the present invention of the genera Ascaris, Toxocara, Toxascaris, Trichuris, is not subject to the above disadvantages. It is non-ir- Syphacia, Aspiculuris, Oxyuris, Nematospiroides and the ritating to mucosal tissue, is essentially tasteless, and can like. it is best administered in association with an inert be administered readily in the form of suspensions, tabdiluent or carrier which may be either solid or liquid in lets, or powders, or as a feed additive. In addition, the nature. Thus the new compound may be utilized in novel compound of the invention possesses a spectrum of dosage forms such as compressed tablets, capsules, or anthelmintic activity which is markedly broader than, and aqueous suspensions. A particularly valuable method superior to, that of the known 2,4,5-trichlorophenol. of administering the product in veterinary medicine con- The novel 2,4,5-tr-ichlorophenol compound of the insists in admixing it with the normal food ration of the vention can be conveniently prepared by reacting one animal concerned. Due to the fact that it is practically molecular equivalent of a soluble 3-ethyl-2-[3-(3-ethyltasteless, it is taken readily when administered in this Z-benzothiazolinylidene) propenyl] benzothiazoliurn comform; a distinct advantage over the known 2,4,5 -.trichloropound having the formula phenol. 1

The following examples illustrate the invention. S GH=OH-OH s v 7 Example 1 1 0 0 A solution of 59 g. (0.30 mole) of 2,4,5-tr1chloro- L l phenol in 100 ml. of methanol is added to a solution of 60 32 g. (0.06 mole) of 3-ethyl-2-[3-(3-ethyl-2-benzothia- C2H5 O2H5 zolinylidene) propenyl] lbenzo'thiazolium patoluenesul- I fonate in '500 ml. methanol. 10 ml. (0.06 mole) of 6 N with at least 3 molecular equivalents of 2,4,5-trichloroaqueous sodium hydroxide is added, followed by 200 phenol. 1n the above formula A- represents the hydroxml. of water at 60 C. A red oil separates immediately ide ion or an anion of an acid. The term soluble comwhich crystallizes on cooling. The reaction mixture is pound is used here in a relative sense and means a deallowed to stand overnight, the crystalline solid collected gree of solubility substantially greater than that exhibited by filtration and washed with 50 ml. of aqueous methanol by the novel 2,4,5-trichlorophenol compound of the in- (1 vol. water: 3 vol. methanol). The product is dissolved vention. Some examples are 3-ethyl-2-[3-(3-et-hyl-2- benin 1100 ml. of hot methanol, 5.6 g. of 2,4,5-trich1oroz-othiazolinylidene) propenyl] benzothiazolium chloride, phenol added, followed by ml. of warm water (60 bromide, iodide, perchlorate, thiocyanate, ethosulfate, C.) and the mixture allowed to cool. The precipitate acetate, benzenesulfonate, and p-toluensulfonate. Some which forms on cooling is collected by filtration, washed with aqueous methanol (1:6 by volume), and dried in freshly prepared silver oxide (silver hydroxide). The vacuo at 50 C. The product has the formula resulting mixture of silver salts is separated by filtration o ()H OH=CI-IOH C1 ll l r N C1- C1-- C H O H L I and melts at l357 C. through diatomaceous earth and the filtrate which con- By substituting 26.8 g. of 3-ethyl-2-[3-(3-ethyl-2-bentains the 3-ethyl-2-[3-(3-ethyl-2 -benzothiazolinylidene) zothiazoli-nyl-idene) propenyl] benzothiazolium bromide propenyl] benzothiazolium hydroxide is added to a hot for the 32 g. of the 3-ethyl-2-[3-(3-ethyl-2-benzothiasolution of g. of 2,4,5atrichlorophenol dissolved in zolinylidene) propenyl] benzothiazolium p-toluenesulfo- 120 ml. of methanol. ml. of water is then added and nate used in the above procedure one obtains the same the reaction mixture allowed to stand overnight. The product. crystalline solid is collected by filtration, recrystallized The 3 ethyl 2 [3+(3-ethyl-2-benzothiazolinylidene) from aqueous methanol and dried in vacuo at 50 C. to propenyl] benzothiaz-olium p-toluenesulfonate used as obtain the desired product which has the formula given in starting material in the above procedure may be prepared 9 Example 1; MP. 1346 C. in the following manner: A mixture of 300 g. of (2.0 If desired, 10 g. of finely-divided, freshly prepared silmoles) of Z-methylbenzothiazole and 450 g. (2.25 moles) ver carbonate may be substituted for the 10 g. of silver of ethyl p-toluenesulfonate is heated to about 140-50 oxide in the foregoing procedure. C. at which temperature an exothermic reaction occurs What is claimed is: and external heating is removed. After the temperature The 2,4,5-trichlorophenol compound of the formula 0- OH S GH=CHOH S l O O H l 2 N+ N C1- CI C1115 C2115 (E 1 G1 stops rising, heating is resumed and the temperature of References Cited in the file of this patent the reaction mixture maintained in the range between 140190 C. for a total of one and one-half hours. Upon UNITED STATES PATENTS cooling, the reaction mixture crystallizes. The crystal- 2345349 Brook J1me 1941 line mass is triturated with ethyl acetate, filtered, di 2,245,250 Brook June 1941 solved in 1 liter of hot alcohol and enough warm ethyl 2393914 Mcoowen at July 1959 acetate added to make a total volume of 6 liters. The Elslager at 1960 mixture is cooled to 10 C., the precipitate collected by FO N PATENTS filtration, washed with ethyl acetate, and dried in vacuo a at 65 C. The methylbenzothiazole-etho-p-toluenesulgreat :i g g fonate so prepared melts at 162-4 C. ustm 1a A mixture of 105 g. (0.3 mole) of methytbenzoth-ia- OTHER REFERENCES zole-etho-p-toluenesulfonate, 90 g. (0.6 mole) of triethyl orthoformate and 330 ml. of pyridine is refluxed with rapid stirring for one and one-fourth hours and allowed to cool overnight. .The precipitate is collected by filtration, Washed with Water, and recrystallized from a mixture of 7500 ml. of methanol and 700 ml. of water to obtain the desired 3-ethyl-2-[3-(3-ethyl-2-benzothiazolinylidine) p'ropenyl] benzothiazolium pwtoluenesulfonate which melts at C.; M.P. 2689 C. after drying in Chem. Abstracts, vol. 28, col. 4712 (1934).

Lamson et al.: J. of Pharm. and Experimental Therapeutics, vol. 56, pp. 60 to 62 (1936).

Chem. Abstracts, vol. 34, .cols. 4069-4070 (1940).

50 Martin: Am. Journ. Vet. Res., vol. 11, pp. 58 to 69 Venkataram: The Chemistry of Synthetic Dyes, vol. II, pages 1 1-57 and 1185-86, Academic Press Inc., New York (1952).

vacuo' Example 2 Perez-Santiago: The Amer. J our. of ,Tropical Medicine and Hygiene, vol. 2, N0. 2, pp. 307 to 310 (1953). A hot, filtered solution of 5 g. of 3-ethyl-2-[3-(3-ethyl- Elsevier: Chemistry of Carbon Compounds, vol. IIIA, 2-benzothiazolinylidene) propenyl] benzothiazolium bropage 439, Elsevier Pub. Co., New York (1954). mide in a mixture of 100 ml. methanol and 5 ml. water Swartzwelder et :al: Journ. Am. Med. Assoc., vol. 165,

is shaken with a suspension of 10 g. of finely-divided, pages 2063 to 2067 (December 21, 1957). 

